卵巢癌是妇科常见恶性肿瘤之一，死亡率居妇科肿瘤首位，而针对其治疗研究进展不大。本课题组对79例卵巢癌患者常见22个基因216个位点突变进行研究，发现13.9%存在c-Met N375S突变，且其预后明显差于未突变者。进一步研究发现，在Plexin B1特异性配体Semaphorin 4D的作用下，c-Met N375S突变的卵巢癌细胞的迁移能力明显强于野生型，且其细胞中c-Met与Plexin B1的结合明显减弱。本课题拟进一步扩大样本研究卵巢癌中c-Met N375S突变的频率，研究c-Met N375S突变对c-Met与Plexin B1相互作用的影响，对Plexin B1/Rho A、c-Met下游信号通路和卵巢癌细胞侵袭转移、增殖能力等的影响，探讨这一系列生物学过程与c-Met-Plexin B1结合的关系，从而为出现c-Met N375S突变的卵巢癌患者提供新的治疗思路。

Ovarian cancer is one of the most common female cancer, ranking the first in mortality in women. Effective new therapeutic strategy of ovarian cancer is still under exploring. After researching 216 locus mutations of 22 genes, we found that 11 in 79 patients had c-Met N375S mutation and their survival was poorer. Our study further indicated that with the stimulation of Semaphorin 4D, the ligand of PlexinB1, the migration ability of c-Met N375S ovarian cancer was enhanced and the binding between c-Met and Plexin B1 was reduced. In this proposal, we aim to study the interation between c-Met N375S and Plexin B1, furthermore uncover the mechanism of c-Met N375S mutation affecting biological behaviors of ovarian cancer cells. This study may pave the way for new treatment of ovarian cancer patients suffering with c-Met N375S locus mutation.